Monday, July 23, 2007

Derivation of pluripotent epiblast stem cells from mammalian embryos

In this paper, a novel type of stem cells are described, the epiblast stem cells (EpiSCs), derived from late rodent epiblast layers and discovered for its ability to grow in a chemically defined medium (CDM) containing activin A and FGF2 (CDM/AF), forming colonies with characteristics of pluripotent cells, and expressing markers of pluripotency; thus they differ from mouse ES cells not only in their tissue of origin, but also in their pluripotency pathway (activin/Nodal). Four levels of characterization confirmed the uniqueness of EpiSCs: first, a morphological analysis of cultures; second, EpiSCs were analyzed both with qualitative (PCR, immunostaining) and quantitative (q-PCR) methods, confirming that they were neither mouse ES cells nor primordial germ cells; third, microarray expression patterns of EpiSCs resembled their original layer; and finally, the pluripotency of these cells was assessed both in vivo (injected colonies were able to produce teratomas containing several types of tissues -confirming that EpiSCs have a multi- lineage pluripotency) and in vitro (EpiSCs differentiated into a wide variety of cell types). Clonal sublines produced similar results. Interestingly, EpiSCs share with human ES cells many differences with mouse ES cells that were previously attributed to species divergence, for example their epigenetic stability, that could reflect a similar epiblast origin. This was the editor's summary for this and a related paper that appeared in the same issue of Nature:
A new type of stem cell. Human embryonic stem (ES) cells are potentially important in therapy because they are pluripotent, capable of differentiating into virtually any cell type given appropriate encouragement. One obstacle to progress in research on them has been the baffling differences between human and mouse ES cells. Now two groups working independently have created a new kind of pluripotent ES cell. Derived from mouse embryos after they implant in the wall of the uterus, these EpiSCs (epiblast stem cells) are distinct from 'classic' mouse ES cells and mirror key features of human ES cells. The discovery of EpiSCs should provide an important experimental model to accelerate the use of human ES cells in research and eventually perhaps, in therapy.
Brons IGM. et al. 2007. Nature 448:191-195

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